Supportive Care Group Research Articles

Assessment of Quality of Life in the Supportive Care Setting of the Big Lung Trial in Non–Small-Cell Lung Cancer

The Big Lung Trial (BLT) was a large, pragmatic trial to evaluate the addition of chemotherapy to primary treatment (ie, surgery, radical radiotherapy, or supportive care) in non-small-cell lung cancer (NSCLC). In the supportive care group, there was a small but significant survival benefit in patients treated with chemotherapy compared with supportive care alone (no chemotherapy). A substudy was undertaken to evaluate the quality of life (QoL) implications of the treatment options. QoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires C30 (QLQ-C30) and LC17, and daily diary cards. EORTC QLQ-C30 and LC17 were collected at 0, 6 to 8, 12, 18, and 24 weeks. Diary cards were completed during the first 12 weeks of the study. The primary end point was global QoL at 12 weeks. A total of 273 patients were randomly assigned: 138 to no chemotherapy and 135 to chemotherapy. There was no evidence of a large detrimental effect on QoL of chemotherapy. No statistically significant differences in global QoL or physical/emotional functioning, fatigue and dyspnea, and pain were detected at 12 weeks. Higher rates of palliative radiotherapy in the no chemotherapy arm may have lessened differences in QoL. Global QoL, role functioning, fatigue, appetite loss, and constipation were prognostic indicators of survival at 12 weeks. There were no important adverse effects of chemotherapy on QoL.

Antibiotics do not reduce toothache caused by irreversible pulpitis

Cochrane Oral Health Group Trials Register and the Pain, Palliative Care and Supportive Care Group Trials Register, the Cochrane Central Register of Controlled Trials, Medline and Embase. Randomised controlled trials (RCT) were included that involved patients over the age of 18 years who had presented with a single tooth with a clinical diagnosis of irreversible pulpitis. Abstracts of studies were independently assessed by two reviewers. The primary outcome was patient-reported pain (intensity/duration) and pain relief measured on a categorical scale in the preoperative phase of irreversible pulpitis. Secondary outcomes were type, dose and frequency of medication required for pain relief. Only one trial was included so pooling of data from studies was not possible and a descriptive summary is presented. One trial of 40 participants was included. There was a close parallel distribution of the pain ratings in both the intervention and placebo groups over the 7-day study period. The between-group differences in sum pain intensity differences for the penicillin group were 6.0+/-10.5, and for placebo 6.0+/-9.5 (P=0.776; differences assessed by Mann-Whitney-Wilcoxon test considered to be statistically significant at P=0.05). The sum pain percussion intensity differences for the penicillin group were 3.5+/-7.5 and placebo 2.0+/-7.0 (P=0.290). There was no significant difference in the mean total number of ibuprofen tablets (P=0.839) and acetaminophen tablets (P=0.325) taken for pain relief in either group over the study period. The administration of penicillin over placebo did not appear to significantly reduce the quantity of analgesic medication taken (P=0.05) for irreversible pulpitis. This review based on one methodologically sound but low-powered small sample trial, provides some evidence that there is no significant difference in pain relief between individuals who had untreated irreversible pulpitis who did or did not take antibiotics in addition to analgesics.

Transcatheter Arterial Chemoembolization Therapy for Patients With Hepatocellular Carcinoma: A Case-Controlled Study

Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival. Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care. The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis. TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.

Vaccination with EGF active immunotherapy improves survival in advanced non small cell lung cancer (NSCLC) patients: Interim analysis of a randomized phase II trial

7210 Background: During the last 9 years, numerous clinical trials have been conducted testing an Epidermal Growth Factor (EGF) active immunotherapy approach in patients with advanced NSCLC. This approach consists of human EGF linked to a carrier protein and administered in an adjuvant. Specifically, the vaccine is composed of human recombinant EGF conjugated to Neisseria meningitides P64K as carrier protein and emulsified in Montanide ISA51. Here, we report partial results from an open label, randomized Phase II trial designed to test immunogenicity, safety and efficacy of the EGF vaccine. Methods: Two groups of unresectable, stage IIIb or IV NSCLC patients were compared. All patients received first line chemotherapy and were then randomized to receive EGF vaccine (Group 1) or best supportive care (Group 2). Each dose contained 50ug EGF administered on days 0, 7, 14, 21, 51 and then monthly. Sera anti-EGF antibody titers as well as plasma EGF concentration [EGF] were measured monthly. Survival was compared between treatment groups. Results: Sixty nine (69%) of vaccinated patients (Group 1) showed seroconversion defined as antibody titer levels at least 2X baseline, while 23% of controls (Group 2) did. Forty five percent (45%) of vaccinated patients had a good antibody response (at least 4X baseline levels and at least 1:4000 sera dilution) while none of the controls did. The geometric mean of maximal antibody titers in Group 1 was 1: 2756 and 1:316 in Group 2. Mean minimal [EGF] was 20 pcg/ml for Group 1 and 60 pcg/ml for Group 2. No serious adverse events were reported. Vaccinated patients survived significantly longer than controls. Group 1 median overall survival was 8.47 months (mean 11.52 months) while Group 2 median overall survival was 4.33 months (mean 7.41 months) (p=0.028). Conclusions: Vaccination with EGF active immunotherapy was safe, immunogenic, and significantly increased survival of advanced NSCLC patients in this study. Further study of this approach is warranted. No significant financial relationships to disclose.

The Cochrane Pain, Palliative and Supportive Care Group: current reviews and work in progress

The Cochrane Pain, Palliative and Supportive Care Group: current reviews and work in progress

Second-line chemotherapy in recurrent small cell lung cancer: Results from a crossover schedule after primary treatment with cisplatin and etoposide (EP-regimen) or cyclophosphamide, epirubicin, and vincristin (CEV-regimen)

To evaluate the benefit of crossover chemotherapy with etoposide and cisplatin (EP) versus cyclophosphamide, epirubicin, vincristine (CEV) at relapse after primary treatment with the opposite regimen in patients with small cell lung cancer (SCLC). Further, to compare the crossover group with patients not receiving chemotherapy. Among 286 patients diagnosed with relapse after first-line chemotherapy, 120 patients received second-line chemotherapy and 166 patients received best supportive care. Fifty-six patients received EP after previous treatment with CEV, 52 received CEV after EP, and 12 patients were re-treated with the same regimen. Possible prognostic factors in the crossover group were identified at time for first-line chemotherapy and at relapse. The EP therapy comprised five courses of etoposide 100 mg/m(2) IV and cisplatin 75 mg/m(2) IV on day 1, followed by oral etoposide 200 mg/m(2) daily on day 2-4. The CEV-regimen was five courses of epirubicin 50 mg/m(2), cyclophosphamide 1000 mg/m(2), and vincristine 2 mg, all IV on day 1. Patients administered second-line chemotherapy lived significantly longer with median survival 5.3 months compared to 2.2 months in patients with best supportive care only (P<0.001). The best supportive care patients had significantly worse PS status and more resistant disease. The crossover treatment group was well balanced regarding possible prognostic factors prior to initial treatment and at recurrence. No difference in survival was found (P=0.71). Univariate analysis revealed PS at recurrence, objective tumour response from initial chemotherapy, disease stage at first-line, LDH-, NSE-, and ALP at first-line to be significant prognostic factors for survival in the second-line setting. In a multivariate analysis, only PS at time of recurrence remained an independent prognostic factor (P<0.0001). Patients administered second-line chemotherapy had significantly longer survival than patients administered best supportive care. However, this difference can be explained by more negative prognostic factors in the best supportive care group. No survival difference between EP and CEV crossover chemotherapy was found. Multivariate analysis revealed PS at time of relapse as the only independent predictor of survival in the crossover recurrent SCLC group.

Management of Acute Myeloid Leukemia (AML) in First Relapse: Retrospective Analysis about 101 Adults Cases Receiving Homogeneous First-Line Therapy. Impact of Prognostic Factors and Treatment.

We retrospectively analyzed impact of prognostic factors and salvage therapy in 101 patients (pts) with AML in 1st relapse. All pts were treated as 1st line according protocols GOELAMs 1 (87–94) or 2 (95–99). They all achieved complete remission after one (85%) or two (16%) induction with a combination of anthracycline and cytarabine. Consolidation therapy included one course of high-dose cytarabine (HiDAC) and a second consolidation (amsacrine-VP16) or, for a subset of pts, intensification with allogeneic or autologous stem cell transplantation (SCT). Data were collected in 3 of the centers participating to these trials. Main characteristics of pts at initial diagnosis were: median age : 39 y (range 17–64); sex : 55 male, 46 female; WBC count > 30 000/μl in 42 (42%) pts; 16/85 (18%) pts had unfavorable karyotype. Median duration of 1st complete remission (CR1) was 10 months (range: 1–101). Duration of CR1 was shorter than 6 months in 22 (22%) pts, between 6 and 12 months in 41 (40%) pts and longer than 12 months in 38 (38%) pts. At time of 1st relapse, median age was 40 y (range 18–66) and 10/38 (26%) unfavorable karyotype.There were no specific recommendations in the GOELAMs protocols for the second line therapy: modalities of treatment were therefore left to investigator's decision. First step of relapse treatment was based on intensive chemotherapy in 79 (79%) pts including 55 pts who received a regimen containing HiDAC (Group 1) and 24 pts who received a chemotherapy without HiDAC (Group 2). Eight pts received an autologous SCT (4 pts) or an allogeneic SCT (4 pts) without any previous salvage chemotherapy (Group 3). One pt received gemtuzumab ozogamicin and thirteen pts received only oral chemotherapy and/or supportive care (Group 4).Fifty-seven pts (56%) achieved a second CR. Response rate and median survival according to initial therapy of relapse are shown in the following table. Differences are not significant.Complete response (%)Median survival (months)Group 1 (n = 55)39 (71%)11.5Group 2 (n = 2410 (42%)8Group 3 (n = 8)6 (75%)7.5Group 4 (n = 14)2 (14%)3.5Twenty seven pts out of the 49 pts who achieved a CR2 after intensive chemotherapy (Group 1 and 2) received subsequent intensification with either an allogeneic SCT (7 pts) or an autologous SCT (20 pts). Median survival of these pts subsequently transplanted was 18 months compared to only 10 months in the 22 pts of group 1 and 2 who did not receive a subsequent transplantation. Difference is not significant (log rank test, p = 0.65). Nine (33%) of the 27 transplanted pts are alive more than 36 months after relapse (range 41–120).Univariate analysis demonstrated that adverse prognosis factors on survival at 1st relapse were duration of RC1 shorter than 12 months (p= 0.005)and complex cytogenetic abnormalities (p= 0.0086).Conclusion: Intensive chemotherapy including HiDAC at 1st relapse in AML in adults provided a high rate of complete response. Intensification with SCT after CR2 was obtained can provide a very long survival in a limited number of pts. At 1st relapse, adverse prognostic factors on survival were short CR1 and unfavorable karyotype. Risk-adapted of AML in first relapse may therefore be warranted. [Display omitted]

Vaccination with epidermal growth factor (EGF) for non small cell lung cancer (NSCLC) therapy: Preliminary results from a randomized phase II clinical trial

2514 Background: Epidermal growth factor (EGF) plays an important role in the regulation of tumor growth. Our approach consists of active immunization with human recombinant EGF coupled to a carrier protein and adjuvanted in Montanide to induce EGF deprivation. Here we report the preliminary results of a randomized Phase II trial designed to test the efficacy of the EGF cancer vaccine in stage IIIb/IV NSCLC patients. Methods: Two groups of 40 unresectable NSCLC patients were compared. All patients received first line chemotherapy and then were randomized to receive the EGF cancer vaccine (group 1) or best supportive care (group 2). Patients were vaccinated on days 0, 7, 14, 21, 51 and then monthly. Anti-EGF antibody titers and EGF concentration ([EGF]) in sera were measured. Results: Fifty patients have been included in the trial (25 vaccinated and 25 controls). Seventy (70) % of the vaccinated patients have shown seroconversion, defined as at least 2X the original antibody titer while 40 % of controls have shown a 2X increase of the natural anti-EGF antibody titers in the follow-up time. However, 50% of the vaccinated subjects developed a good antibody response (GAR), defined at least 4 times above baseline and 1:4000 titer while none of the controls did. The geometric mean of maximal antibody titers was 1: 3500 for group 1 and 1:462 for Group 2. Mean minimal [EGF] was 20 pg/ml for group 1 and 60 pg/ml for group 2. A significant increase in survival was obtained for GAR patients as compared with poor responders. A trend to increase in survival was observed for group 1 (median 8.47 months) as compared with group 2 (median 5.47 months). Conclusions: Preliminary results from a randomized Phase II trial corroborate the immunogenicity and safety of EGF cancer vaccine and the relationship between anti-EGF response and survival of advanced NSCLC patients. No significant financial relationships to disclose.

Vaccination with epidermal growth factor (EGF) for non small cell lung cancer (NSCLC) therapy: Preliminary results from a randomized phase II clinical trial

2514 Background: Epidermal growth factor (EGF) plays an important role in the regulation of tumor growth. Our approach consists of active immunization with human recombinant EGF coupled to a carrier protein and adjuvanted in Montanide to induce EGF deprivation. Here we report the preliminary results of a randomized Phase II trial designed to test the efficacy of the EGF cancer vaccine in stage IIIb/IV NSCLC patients. Methods: Two groups of 40 unresectable NSCLC patients were compared. All patients received first line chemotherapy and then were randomized to receive the EGF cancer vaccine (group 1) or best supportive care (group 2). Patients were vaccinated on days 0, 7, 14, 21, 51 and then monthly. Anti-EGF antibody titers and EGF concentration ([EGF]) in sera were measured. Results: Fifty patients have been included in the trial (25 vaccinated and 25 controls). Seventy (70) % of the vaccinated patients have shown seroconversion, defined as at least 2X the original antibody titer while 40 % of controls have shown a 2X increase of the natural anti-EGF antibody titers in the follow-up time. However, 50% of the vaccinated subjects developed a good antibody response (GAR), defined at least 4 times above baseline and 1:4000 titer while none of the controls did. The geometric mean of maximal antibody titers was 1: 3500 for group 1 and 1:462 for Group 2. Mean minimal [EGF] was 20 pg/ml for group 1 and 60 pg/ml for group 2. A significant increase in survival was obtained for GAR patients as compared with poor responders. A trend to increase in survival was observed for group 1 (median 8.47 months) as compared with group 2 (median 5.47 months). Conclusions: Preliminary results from a randomized Phase II trial corroborate the immunogenicity and safety of EGF cancer vaccine and the relationship between anti-EGF response and survival of advanced NSCLC patients. No significant financial relationships to disclose.

Review: single dose, oral paracetamol reduces moderate to severe postoperative pain

Barden J, Edwards J, Moore A, et al . Single dose oral paracetamol (acetaminophen) for postoperative pain. Cochrane Database Syst Rev 2004;(1):CD004602 (latest version 25 Nov 2003). Q Is single...

Methadone for cancer pain.

Methadone is an opioid used in the management of cancer pain both in opioid naïve patients and in rotation from other opioids. A particular role in neuropathic pain has been suggested. The quest for evidence based palliative care prompted a formal appraisal of methadone in comparison with other analgesics. To determine the effectiveness and safety of methadone analgesia in cancer pain patients. MEDLINE (1966 to August 2002), EMBASE (1980 to August 2002), CancerLit (1993 to August 2002), CINAHL (1982 to August 2002) and Cochrane databases were searched using a strategy developed with the Cochrane Pain, Palliative and Supportive Care Group. Assiduous efforts were made to identify unpublished or current trial work. Randomised controlled trials of methadone against active or placebo comparator in patients with cancer pain were included. Outcome measures sought were reduction in pain intensity measured by an appropriate scale, adverse effects, attrition, patient satisfaction and quality of life. There were no language restrictions. Absence of patient reported data was an exclusion criterion. Eligible studies were selected with independent collaboration from a colleague in Bristol (AND). Full text was retrieved if any uncertainty about eligibility remained. Non-English texts were screened by Cochrane contacts aware of the eligibility criteria. Quality assessment and data extraction were conducted using standardised data forms. Drug and placebo dose, titration, route and formulation were compared and detail of all outcome measures (if available) recorded. Eight randomised controlled trials (five double blinded, two crossover) with 356 recruits and 326 completing patients were included. All involved active placebo (five morphine, one dextromoramide or pethidine, one diamorphine with cocaine mixture). All employed different starting doses, titration regimens and pain scoring scales. Few presented complete pain data sets and no meta-analysis has been possible. No differentiation by cancer pain syndrome was made. Complete adverse events data were recorded in every study, and were similar in incidence and severity to those experienced with morphine. There is evidence to suggest that methadone is an analgesic with similar efficacy to morphine and a comparable side effect profile. However, the majority of studies involved single dose comparisons or short term use. This methodology fails to reproduce clinical practice. Therefore there is a very significant danger that the effects of methadone accumulation leading to delayed onset of adverse effects which occurs with chronic administration has not been represented. Fixed interval dosing schedules conducted over several days are associated with a high risk of serious morbidity and mortality. There is no trial evidence to support the proposal that methadone has a particular role in neuropathic pain of malignant origin. Conclusions have been limited by the variations in trial design, dosing regimens and limited presentation of primary outcome data. The complex and highly individual pharmacokinetics of methadone require that experienced clinicians take responsibility for initiating, titrating and monitoring this drug.

Single dose oral paracetamol (acetaminophen) for postoperative pain.

Paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the relief of mild and moderate pain arising from headache, musculoskeletal conditions and dysmenorrhoea. A prior Cochrane systematic review concluded that paracetamol is also effective for postoperative pain, but additional trials have since been published. This review sought to evaluate the efficacy and safety of paracetamol using current data, and to compare the findings with other analgesics evaluated in the same way. To assess the efficacy of single dose oral paracetamol for the treatment of acute postoperative pain. We searched the Cochrane Library (Issue 3, 2002), the trials register of the Cochrane Pain, Palliative and Supportive Care group (November 2002); MEDLINE (1966 to May 1996); PubMed (1996 to August 2001); EMBASE (1980 to 1996); the Oxford Pain Relief Database (1950 to 1994); and reference lists of articles in order to update an existing version of the review. Randomised, double-blind, placebo-controlled clinical trials of paracetamol for acute postoperative pain in adults. Two reviewers independently assessed trial quality and extracted data. The area under the 'pain relief versus time' curve was used to derive the proportion of patients with paracetamol or placebo experiencing least 50% pain relief over four to six hours using validated equations. The number-needed-to-treat (NNT) was calculated using 95% confidence intervals. Information on adverse effects was also collected. Forty-seven reports that enrolled 4186 patients (2561 patients were treated with a single oral dose of paracetamol and 1625 with placebo) met the inclusion criteria and were included in the analyses. The NNTs for at least 50% pain relief over four to six hours following a single dose of paracetamol were as follows: 325 mg NNT 3.8 (2.2 to 13.3); 500 mg NNT 3.5 (2.7 to 4.8); 600/650 mg NNT 4.6 (3.9 to 5.5); 975/1000 mg NNT 3.8 (3.4 to 4.4); and 1500 mg NNT 3.7 (2.3 to 9.5). Sub-group analysis showed no significant differences between smaller and larger trials, or lower and higher quality trials. Drug-related study withdrawals were rarely reported. Studies reported a variable incidence of adverse effects that were generally mild and transient. There were no statistically significant differences in the frequency of reported adverse effects between paracetamol 975/1000 mg and placebo. Single doses of paracetamol are effective analgesics for acute postoperative pain and give rise to few adverse effects.

Feverfew for preventing migraine.

Feverfew (Tanacetum parthenium L.) extract is a herbal remedy used for preventing attacks of migraine. To systematically review the evidence from double-blind randomised controlled trials (RCTs) assessing the clinical efficacy and safety of feverfew versus placebo for preventing migraine. Publications describing (or which might describe) double-blind RCTs of feverfew extract for migraine were sought through the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2003); PREMEDLINE/MEDLINE (1966 to July 2003); EMBASE (1974 to July 2003); the trials register of the Cochrane Pain, Palliative and Supportive care group (July 2003); and AMED (1985 to July 2003). Manufacturers of feverfew were contacted and the bibliographies of identified articles checked for further trials. Randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew for preventing migraine were included. Trials using clinical outcome measures were included. Trials focusing exclusively on physiological parameters were excluded. There were no restrictions regarding the language of publication. Data on patients, interventions, methods, outcome measures, results and adverse events were extracted systematically. Methodological quality was evaluated using the scoring system developed by Jadad and colleagues. Two reviewers independently selected studies, assessed methodological quality and extracted data. Disagreements concerning evaluation of individual trials were resolved through discussion. Five trials (343 patients) met the inclusion criteria. Results from these trials were mixed and did not convincingly establish that feverfew is efficacious for preventing migraine. Only mild and transient adverse events were reported in the included trials. There is insufficient evidence from randomised, double-blind trials to suggest an effect of feverfew over and above placebo for preventing migraine. It appears from the data reviewed that feverfew presents no major safety problems.

The Cochrane Pain, Palliative and Supportive Care Group: life history of a Cochrane review.

The Cochrane Pain, Palliative and Supportive Care Group: life history of a Cochrane review.

Oral morphine for cancer pain.

Morphine has been used to relieve pain for many years. Oral morphine in either immediate release or sustained release form remains the analgesic of choice for moderate or severe cancer pain. To determine the efficacy of oral morphine in relieving cancer pain. To assess the incidence and severity of adverse effects. The following databases were searched: The Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library, Issue 4, 2002; the trials register of the Cochrane Pain, Palliative and Supportive Care group (February 2002); MEDLINE 1966 to December 2002; EMBASE 1988 to December 2002; and the Oxford Pain Relief database 1950 to 1994. Published randomised controlled trials (full reports) reporting on the analgesic effect of oral morphine in adults and children with cancer pain. Any comparator trials were considered. Trials with fewer than 10 subjects were excluded. One reviewer extracted data, and the findings were checked by two other reviewers. There were insufficient comparable data for meta-analysis to be undertaken, or to produce numbers-needed-to-treat (NNT) for the analgesic effect. Forty five studies (3061 subjects) met the inclusion criteria. Fourteen studies compared oral sustained release morphine (MSR) preparations with immediate release morphine (MIR). Eight studies compared MSR and MSR in different strengths. Nine studies compared MSR with other opioids. Five studies compared MIR with other opioids. Two studies compared oral MSR with rectal MSR. One study was found comparing each of the following: MSR tablet with MSR suspension; MSR with MSR at different dose frequencies; MSR with non-opioids; MIR with non-opioids; oral morphine with epidural morphine; and MIR with MIR by a different route of administration. Morphine was shown to be an effective analgesic. Pain relief did not differ between MSR and MIR. Sustained release versions of morphine were effective for 12 or 24 hour dosing depending on the formulation. Adverse effects were common but only 4% of patients discontinued treatment because of intolerable adverse effects. The randomised trial literature for morphine is small given the importance of this medicine. Most trials recruited fewer than 100 participants, and did not provide appropriate data for meta-analysis. Trial design was frequently based on titration of morphine or comparator to achieve adequate analgesia, then crossing subjects over in crossover design studies. It is not clear if these trials are sufficiently powered to detect any clinical differences between formulations or comparator drugs.

Single fraction radiotherapy is as effective as multiple fractions for palliating painful bone metastases: Abstracted from: Wu JSY, Wong R, Johnston M et al. on behalf of the Cancer Care Ontario Practice Guidelines Initiative Supportive Care Group. Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Rad Oncol Biol Phys 2003; 55: 594–605.

Single fraction radiotherapy is as effective as multiple fractions for palliating painful bone metastases: Abstracted from: Wu JSY, Wong R, Johnston M et al. on behalf of the Cancer Care Ontario Practice Guidelines Initiative Supportive Care Group. Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Rad Oncol Biol Phys 2003; 55: 594–605.

Calcitonin for metastatic bone pain.

Pain is the most frequent symptom experienced by cancer patients, its intensity dependent on the site of the tumour. Tumours that compromise bone or nervous structures due to the bone destruction process are the most painful. There are several treatments to deal with pain (and other symptoms) caused by bone metastasis. The hormone, calcitonin, has the potential to relieve pain, and also retain bone density, thus reducing the risk of fractures. To assess the effectiveness of calcitonin in controlling metastatic bone pain and reducing bone complications (hypercalcemia, fractures and nervous compression) in patients with bone metastases. Electronic searches were performed in MEDLINE (1966-2001), EMBASE (1974-2001), the Cochrane Central Register of Controlled Trials (Issue 2, 2001), specialised registers of the Cochrane Cancer Network and of the Cochrane Pain, Palliative and Supportive Care Group. Registers of clinical trials in progress were also searched. Studies were included if they were randomised, double-blind clinical trials of patients with metastatic bone pain, treated with calcitonin, where the major outcome measure was pain, assessed at four weeks or longer. Study selection and data extraction were performed by two independent reviewers. Only two studies (90 patients) were eligible for inclusion in the review and therefore meta-analysis of the data was not possible. Intention-to-treat analysis was performed by imputing all missing values as adverse outcomes. Of the two small studies included in the review, one study showed a non-significant effect of calcitonin in the number of patients with total pain reduction (RR 2.50; CI 95%, 0.55 to 11.41). The second study provided no evidence that calcitonin reduced analgesia consumption (RR 1.05; CI 95%, 0.90 to 1.21) in patients with painful bone metastases. There was no evidence that calcitonin was effective in controlling complications due to bone metastases; for improving quality of life; or patients' survival. Although not statistically significant, a greater number of adverse effects were observed in the groups given calcitonin in the two included studies (RR 3.35, CI 95%, 0.72 to 15.66). The limited evidence currently available for systematic review does not support the use of calcitonin to control pain from bone metastases. Until new studies provide additional information on this treatment, other therapeutic approaches should be considered.

The Cochrane Pain, Palliative and Supportive Care Group: scope and challenges.

The Cochrane Pain, Palliative and Supportive Care Group: scope and challenges.

Topical agents or dressings for pain in venous leg ulcers.

Venous leg ulcers affect up to 1 per cent of people at some time in their life. These ulcers are often painful and some clinicians choose dressings and topical treatments (analgesia/ local anaesthetic) to reduce the pain both during and between dressing changes. To assess the effectiveness of dressings, local anaesthetics or topical analgesia for pain relief in venous leg ulceration. Cochrane Wounds Group Register and the Cochrane Collaboration Field in Complementary Medicine were searched in June 2002. Cochrane Pain Palliative and Supportive Care Group and Cochrane Wounds Group strategy were combined and used. All randomised controlled trials which evaluated local interventions used to relieve venous leg ulcer pain were considered. Pain was defined as either persistent pain or pain at dressing changes or debridement. Eligibility for inclusion was confirmed by two reviewers who independently assessed the potential trials. Details of eligible studies were summarised using a data extraction sheet which was checked by the second reviewer. No trials evaluating interventions for persistent pain were identified for the initial review in 1999 nor the update in 2002. Three trials were included in the 1999 review comparing a eutectic mixture of local anaesthetic (EMLA) versus placebo for pain at debridement. In 2002 a further 3 trials were available (6 trials in total with 317 patients). The studies were considered sufficiently similar to pool and meta analysis found a statistically significant reduction in debridement pain scores with EMLA 5% cream. EMLA was associated with a reduction in pain scores (measured on a 100 mm scale) of 20.6 mm (95% Confidence Interval 29.11-12.19). One small trial measured healing as an outcome and found no difference in numbers of ulcers healed at the end of the study. EMLA provides effective pain relief for venous leg ulcer debridement however, the effect of the product on ulcer healing is unknown. Research is required to determine the impact of debridement and of EMLA on ulcer healing. There were no trials addressing the treatment of persistent pain (between and at dressing changes) and further research is warranted.

Analysis of Prognostic Factors Related to Survival Time for Patients with Small Cell Lung Cancer

Background :S mall cell lung cancer represents approximately 20% of all lung carcinomas, and it was recognized as poor long term outcome compared with non-small cell lung cancer. So, prognostic factors in small cell lung cancer patients were investigated in order to improve survival rate by proper therapeutic methods. Material and method : The clinical data of 394 patients who diagnosed and treated as small cell lung cancer were analyzed from 1993 to 2001 at the Kosin University Gospel Hospital, retrospectively. Result : There were 314 male patients (79.7%), and 80 female patients (20.3%), the number of limited disease were 177 (44.9%), those of extensive disease were 217 (55.1%). Overall, 366 out of 394 enrolled patients were confirmed to die. The median survival time was 215 days (95% CI : 192-237days). Disease stage, Karnofsky performance state, 5% body weight loss for recent 3 months, chemotherapy regimens, and additive chest radiotherapy were identified as statistically significant factor for survival time. The median survival times of supportive care group, one anticancer therapy, and two or more